Neurobiology of aging
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Neurobiology of aging · Jan 2015
Seemingly unrelated regression empowers detection of network failure in dementia.
Brain connectivity is progressively disrupted in Alzheimer's disease (AD). Here, we used a seemingly unrelated regression (SUR) model to enhance the power to identify structural connections related to cognitive scores. We simultaneously solved regression equations with different predictors and used correlated errors among the equations to boost power for associations with brain networks. ⋯ As AD studies with a large number of diffusion tensor imaging scans are rare, it is important to detect effects in smaller samples using simultaneous regression modeling like SUR. Diagnosis of mild cognitive impairment or AD is well known to be associated with ApoE genotype and educational level. In a subsample with no apparent associations using the general linear model, power was boosted with our SUR model-combining genotype, educational level, and clinical diagnosis.
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Neurobiology of aging · Jan 2015
Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies.
Mild cognitive impairment (MCI) as a precursor of dementia with Lewy bodies (DLB) is the focus of recent research, trying to explore the early mechanisms and possible biomarkers of DLB. Quantitative electroencephalogram (QEEG) methods are able to differentiate early DLB from Alzheimer's disease (AD). The aim of the present study was to assess whether QEEG abnormalities, characterized by dominant frequency <8 Hz and dominant frequency variability >1.5 Hz, typical of early DLB, are already present at the stage of MCI and to evaluate whether EEG abnormalities can predict the development of DLB. ⋯ One hundred percent of MCI-DLB showed EEG abnormalities at admission. Ninety three percent of MCI-AD maintained a normal EEG throughout the study. QEEG may represent a powerful tool to predict the progression from MCI to DLB with a sensitivity and specificity close to 100%.
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Neurobiology of aging · Jan 2015
COQ2 p.V393A variant, rs148156462, is not associated with Parkinson's disease in a Taiwanese population.
A recent collaborative study that combined linkage analysis with whole-genome sequencing of family members of multiplex families with multiple system atrophy (MSA) has identified COQ2 gene as a causative gene for MSA. The common variant, c. T1178C (p. ⋯ The frequency of TC/CC genotype was comparable between PD patients and control subjects (odds ratio: 0.81, 95% confidence interval: 0.42-1.56, p = 0.53). COQ2 p. V393A variant is not a genetic risk factor for PD, suggesting its specificity in disease susceptibility to MSA.
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Neurobiology of aging · Dec 2014
Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease.
The overlapping clinical and neuropathologic features between late-onset apparently sporadic Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and other neurodegenerative dementias (frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jakob disease) raise the question of whether shared genetic risk factors may explain the similar phenotype among these disparate disorders. To investigate this intriguing hypothesis, we analyzed rare coding variability in 6 Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP), in 141 LOAD patients and 179 elderly controls, neuropathologically proven, from the UK. In our cohort, 14 LOAD cases (10%) and 11 controls (6%) carry at least 1 rare variant in the genes studied. ⋯ A237V), absent in controls and both likely pathogenic. Our findings support previous studies, suggesting that (1) rare coding variability in PSEN1 and PSEN2 may influence the susceptibility for LOAD and (2) GRN, MAPT, and PRNP are not major contributors to LOAD. Thus, genetic screening is pivotal for the clinical differential diagnosis of these neurodegenerative dementias.
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Neurobiology of aging · Dec 2014
Frontobasal gray matter loss is associated with the TREM2 p.R47H variant.
A rare heterozygous TREM2 variant p. R47H (rs75932628) has been associated with an increased risk for Alzheimer's disease (AD). We aimed to investigate the clinical presentation, neuropsychological profile, and regional pattern of gray matter and white matter loss associated with the TREM2 variant p. ⋯ R47H atrophy in temporal lobes as described previously. The high frequency of pathologic behavioral symptoms, combined with a preferential frontobasal gray matter cortical loss, suggests that frontobasal and temporal regions could be more susceptible to the deleterious biological effects of the TREM2 variant p. R47H.